The genetic component of susceptibility to
malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural
proteins and
enzymes. In vivo and in vitro data have suggested that
pyruvate kinase deficiency, which causes a nonspherocytic
haemolytic anaemia, could be protective against
malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the
pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for
malaria selective signatures in two sub-Saharan African populations from Angola and Mozambique, in several groups with different
malaria infection outcome. A European population from Portugal, including a control and a
pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated
malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that
malaria selective pressure is acting in this genomic region.